Human Genetics

, Volume 129, Issue 5, pp 573–582 | Cite as

Mutations in Fanconi anemia genes and the risk of esophageal cancer

  • Mohammad R. Akbari
  • Reza MalekzadehEmail author
  • Pierre Lepage
  • David Roquis
  • Ali R. Sadjadi
  • Karim Aghcheli
  • Abbas Yazdanbod
  • Ramin Shakeri
  • Jafar Bashiri
  • Masoud Sotoudeh
  • Akram Pourshams
  • Parviz Ghadirian
  • Steven A. NarodEmail author
Original Investigation


The incidence of esophageal squamous cell carcinoma (ESCC) is very high in northeastern Iran. Previously, we reported a strong familial component of ESCC among Turkmens, who constitute approximately one-half of the population of this region. We hypothesized that the genes which cause Fanconi anemia might be candidate genes for ESCC. We sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 Turkmen cases of ESCC. We identified three heterozygous insertion/deletion mutations: one in FANCD2 (p.Val1233del), one in FANCE (p.Val311SerfsX2), and one in FANCL (p.Thr367AsnfsX13). All three patients had a strong family history of ESCC. In addition, four patients (out of 746 tested) were homozygous for the FANCA p.Ser858Arg mutation, compared to none of 1,373 matched controls (OR = 16.7, 95% CI = 6.2–44.2, P = 0.01). The p. Lys3326X mutation in BRCA2 (also known as Fanconi anemia gene FANCD1) was present in 27 of 746 ESCC cases and in 16 of 1,373 controls (OR = 3.38, 95% CI = 1.97–6.91, P = 0.0002). In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.


Esophageal Cancer Esophageal Squamous Cell Carcinoma Fanconi Anemia Missense Variant Esophageal Squamous Cell Carcinoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Ms. Safura Kor, Mrs. Goharshad Goglani, and Mrs. Mina Bahrami from the case–control study center (Atrak Clinic) in Gonbad city for helping with study subject recruitment. We also appreciate the kind help of Alexandre Belisle from the Genotyping Platform of the Genome Quebec Innovation Centre from McGill University on performing MassARRAY genotyping of this study and Richard Moore from Genome Science Centre in Vancouver, Canada for implementing 30% of the sequencing of this project. The remaining sequencing was done by Genome Quebec Innovation Centre from McGill University. This study was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Digestive Disease Research Center (DDRC), Tehran University of Medical Sciences (TUMS). We thank Drs. Stephen Meyn and Yigal Dror for helpful comments.

Supplementary material

439_2011_951_MOESM1_ESM.doc (646 kb)
Supplementary material 1 (DOC 645 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mohammad R. Akbari
    • 1
    • 2
    • 3
  • Reza Malekzadeh
    • 1
    Email author
  • Pierre Lepage
    • 4
  • David Roquis
    • 4
  • Ali R. Sadjadi
    • 1
  • Karim Aghcheli
    • 1
  • Abbas Yazdanbod
    • 5
  • Ramin Shakeri
    • 1
  • Jafar Bashiri
    • 1
  • Masoud Sotoudeh
    • 1
  • Akram Pourshams
    • 1
  • Parviz Ghadirian
    • 6
  • Steven A. Narod
    • 2
    Email author
  1. 1.Digestive Disease Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran
  2. 2.Women’s College Research InstituteUniversity of TorontoTorontoCanada
  3. 3.Institute of Medical Science, Faculty of MedicineUniversity of TorontoTorontoCanada
  4. 4.Genome Quebec Innovation CentreMcGill UniversityMontrealCanada
  5. 5.Department of Internal MedicineArdabil University of Medical ScienceArdabilIran
  6. 6.Epidemiology Research Unit Research Centre, CHUM-Hôtel-DieuUniversity of MontrealMontrealCanada

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